BayGenomics has used gene-trap vectors to inactivate thousands of genes in mouse embryonic stem (ES) cells. More than 8000 cell lines with well-characterized insertional mutations have been generated and posted on our website (http:// baygenomics.ucsf.edu./). The ES cells have been made freely availble to the scientific community for the purpose of generating knockout mice. Thus far, we have responded to the requests for more than 930 different ES cell lines. The vast majority of our mutant ES cell lines yield germline-transmitting chimeras, and hundreds of knockout mice have been generated by our group and outside laboratories. Many of the knockout mice are highly relevant to cardiopulmonary disease and development. BayGenomics has also produced two widely used programs for analyzing microarray expression data according to biochemical pathways (GenMAPP and MAPPFinder). In addition, BayGenomics investigators have generated and characterized multiple lines of knockout mice for cardiopulmonary development and disease. BayGenomics has an active, high-quality education program. BayGenomics involves two leading San Francisco Bay Area research institutions: The J. David Gladstone Institutes and the University of California, San Francisco. BayGenomics is organized into seven Components: (1) Gene Trapping in Embryonic Stem Cells, (2) Computational Methods and Genomics Education, (3) In Situ Hybridization, (4) Mouse Resource for Lipid Metabolism, (5) Mouse Resoruce for Pulmonary Disease, (6) Mouse Resource for Cardiopulmonary Development and (7) Administration. A major objective of BayGenomics will be to use custom gene-trap vectors to generate 2,500 ES cell lines per year with well characterized insertional mutations (Component 1). Each "trapped" ES cell line will be posted on our website and will be distributed freely to the research community. A second objective will be to improve the annotation of our website and to provide relevant genomics education programs to our users (Component 2). A third objective is to use in situ hybridization studies to define gene-expression patterns for a subset of the trapped genes, making it easier for our group and others to make informed choices about which genes are likely to be relevant to cardiopulmonary development (Component 3). A fourth objective is to generate a limited number of genetically modified mice, for the purpose of defining the relevance of specific genes to cardiopulmonary development and disease (Component 4-6).